Research Report 2005

Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
Polish Academy of Sciences
Rudolfa Weigla 12, 53-114 Wrocław
Research Report – 2005
Laboratory of Tumor Molecular Immunobiology
Head: Professor Leon Strządała, Ph.D.
Normal and pathological development and selection of lymphoid and neuronal
cells
The orphan nuclear receptor Nur77 is a member of the Nur77 family belonging to the
nuclear hormone receptor superfamily of transcription factors. The Nur77 protein (also termed
NGFI-B, TR3, NR4A1) is a mediator of the cellular response to various external stimuli,
leading to the proliferation, differentiation, apoptosis, and synthesis of steroid hormones,
depending on the cell type.
Previously we showed that thymic lymphomas developing spontaneously in mice with
transgenic TCR are resistant to TCR-induced calcium-mediated apoptosis. This blockade is
localized downstream from the induction of Nur77 expression and upstream from the
execution phase of apoptosis. Treatment with FK506 (inhibitor of calcineurin) or HA1004
(inhibitor of serine-threonine kinases) restored the sensitivity of these cells to ionomycininduced apoptosis. We intend to explore the molecular mechanism of Nur77 action in normal
thymocytes as well as the lack of its activity in transformed T cells. We found that in
apoptosis-resistant cells, inomycin-induced Nur77 strongly binds DNA during the first two
hours of response, in contrast to lymphoma cells treated with ionomycin together with FK506
or HA1004, which undergo massive apoptosis. We showed that Nur77 could discriminate
between calcium signals sensitive to FK506 and those sensitive to HA1004, as the inhibitors
differentially regulate the kinetics of Nur77 nuclear import, and FK506, unlike HA1004,
inhibits Nur77 DNA-binding activity. In the presence of HA1004, NBRE binding by Nur77
protein increases with time (6 h vs. 2 h), whereas the final outcome of both inhibitors is
apoptosis of thymic lymphoma cells.
DEPARTMENT OF IMMUNOCHEMISTRY
Head: Professor Czesław Ługowski, Ph.D.
Laboratory of Microbial Immunochemistry and Vaccines
Head: Professor Czesław Ługowski, Ph.D.
Biochemical characteristics of macromolecules involved in immunological
processes
Immunochemical studies of bacterial endotoxins
Bordetella pertussis, an aerobic Gram-negative rod-like bacteria, is the causative agent of
whooping cough (pertussis) in humans. Pertussis is a highly contagious disease involving the
respiratory tract, especially dangerous for infants and young children. One of the virulence
determinants of B. pertussis and the most abundant surface molecule is lipopolysaccharide
(LPS). It plays a major role in host-pathogen interactions and is responsible for endotoxic
activities. B. pertussis produces only two types of LPS, built of a lipid A moiety linked to a
core nonasaccharide or a dodecasaccharide. The LPS of B. pertussis is devoid of an
O-specific polysaccharide chain, represented instead by a single distal trisaccharide, thus
structurally constituting a lipooligosaccharide (LOS). It was of interest to evaluate LOS
epitopes as a target for antibodies that might be protective against biological activities of
B. pertussis. We chose for these experiments the LOS of B. pertussis strain 186, i.e. the wild
strain and the component of the whole-cell pertussis vaccine which has been used in Poland
since 1978.
We determined the structural details of the B. pertussis strain 186 LOS and the antiendotoxin activity of the polyclonal antibodies against the covalent conjugate of the core
terminal pentasaccharide with tetanus toxoid. Antineoglycoconjugate antibodies inhibited the
secretion of TNFα, IL-6 and NO by LOS-stimulated J774A.1 cells. We also performed STD
NMR experiments for the identification of the binding epitope within the investigated
pentasaccharide. We found that it is located predominantly in the distal trisacharide of the
endotoxin. Additionally, by using HR-MAS NMR analysis we were also able to identify the
pentasaccharide directly on intact LOS and distinguish the LOS of B. pertussis strain 186
possessing a core dodecasaccharide from that of strain 606 possessing a core nonasaccharide.
Thus the discovery of a simple method to distinguish between a protective and a nonprotective immune response to B. pertussis infection and defining the additional components
of acellular pertussis vaccine seems very important. We anticipate that it could improve the
efficiency of the vaccine by promoting immune defense that can kill the bacteria and
neutralize the harmful effects of the endotoxin.
Laboratory of Glycoconjugate Immunochemistry
Head: Associate Professor Hubert Krotkiewski, Ph.D.
Immunochemical and genetic studies on human glycophorin and other proteins
active in the immune system
MBP and PLP are the major components of myelin sheaths, accounting for about 30
and 50% of total myelin proteins, respectively. Human MBP exists in four main isoforms
(17.3, 18.5, 20.2, 21.5 kDa) generated by alternative splicing. PLP is a highly hydrophobic
integral membrane protein of oligodendrocytes, and its two isoforms, encoded by one gene,
are generated by alternative splicing: a 26.6 kDa classic form and a 23.5 kDa DM20 protein.
MBP and PLP are the most extensively studied candidate auto-antigens in multiple sclerosis
(MS). We aimed at the isolation and characterization of CHO cell clones with stable
expression of recombinant MBP or PLP. The rationale for using a mammalian system is the
posttranslational modification of the recombinant proteins expressed in CHO cells. The
obtained clones could be a very useful tool for characterizing the immune response in MS.
Plasmids containing cDNA coding for MBP (21.5 kDa) and PLP (26 kDa) were gifts from
Dr. A. Campagnoni (UCLA, LA, USA). cDNAs were transfected into CHO cells using
FUGENE 6 reagent. Several cell clones were isolated by limiting dilution and characterized
by flow cytometry using anti-MBP or anti-PLP monoclonal antibodies. Two CHO cell clones,
A1 and C1, expressing recombinant MBP and PLP, respectively, were further analyzed. After
fixation and permeabilization allowing intracellular antigen staining, the cells were observed
for immunofluorescence in a confocal scanning microscope. Anti-MBP staining of the A1
clone produced extra-nuclear granules uniformly distributed throughout the entire cell body,
indicating the cytoplasmic localization of the recombinant MBP. Anti-PLP staining of the C1
clone revealed punctate circles, reflecting the surface localization of the recombinant PLP.
Both patterns of the stained CHO cells were consistent with the proper cellular localization of
MBP and PLP observed in myelin sheaths. To further verify that MBP and PLP were
expressed in the A1 and C1 clones, PCR analysis was performed using as a template cDNA
reverse transcribed from the mRNA expressed in either clone. Bands of the predicted sizes,
794 bp for MBP and 528 bp for PLP, were obtained for the A1 and C1 clones, respectively;
they were absent in an analysis of non-transfected CHO cells.
We have expressed and purified a chimeric protein, Fya-GPA, composed of the aminoterminal extracellular domain of the Duffy antigen (aa 3-60) and the C-terminal intracellular
fragment of glycophorin A (GPA, aa 104-131). cDNA constructs encoding chimeric Duffy
protein were cloned into two expression vectors: pComb3H and pGEX, and were expressed in
bacteria. Proteins expressed in bacteria containing a hexahistydyl tag or glutathione-Stransferase (GST) tag were purified by affinity chromatography on Ni-NTA-agarose or on
glutathione-agarose, respectively. Two forms of recombinant protein (Fya-GPA and FybGPA) were obtained containing two different tags: hexahistydyl or GST. Recombinant
proteins containing Duffy epitopes may be very useful in the production and characterization
of monoclonal antibodies.
Carcinoembryonic antigen (CEA) is a well-characterized human tumor-associated antigen
overexpressed by adenocarcinomas, primarily of the colon, rectum, breast, and lung. CEA
functions in vitro as a Ca2+ independent, homo/heterotypic intercellular adhesion molecule
which may play a role in cancer progression and metastasis via promotion of the aggregation
of human colorectal carcinoma cells to liver and lung. CEA and CEA-related glycoproteins
belong to the immunoglobulin superfamily (IgSF), which comprises a set of proteins involved
in cell surface recognition events. We focused on the CEA-oligomerization mechanism.
Twelve different CEA recombinant fragments, ranging from 80 (CEA/1-80) to 120 (CEA/1100, -105, -110, -115, -116, -117, -118, -119 and -120) amino acids, were expressed in
bacteria cells. We cloned cDNA of the CEA fragments into the pGEX vector which contains
C-terminal His- and GST-tags. The recombinant CEA fragments were purified by affinity
chromatography on agarose columns with immobilized Ni2+ (NTA-agarose) and glutathioneSepharose. The degree of purification of the recombinant CEA fragments was evaluated
electrophoretically (SDS-PAGE); the presence of CEA peptides was confirmed by
immunoblotting with polyclonal anti-CEA antibodies. Our observations suggest that the CEA
fragment 115-120aa is a potential inhibitor of homophilic CEA-dependent cell adhesion.
Laboratory of General Immunochemistry
Head: Associate Professor Maria Janusz, Ph.D.
Studies on the mechanism of action of a proline-rich polypeptide complex (PRP)
as an modulator of immunoneurological processes
A proline-rich polypeptide complex (PRP) and its nonapeptide fragment (NP) did not
induce reactive oxygen species secretion in human peripheral blood mononuclear cells
(PBMCs). However, both PRP and NP, when applied to the cells simultaneously with PMA,
inhibited (40-60%) the H2O2-inducing activity of PMA in a dose-dependent manner. The
inhibitory effect of PRP/NP on H2O2 secretion correlates very well with the inhibitory effect
of the peptides on superoxide dismutase (SOD) activity in PBMCs. Many processes in the
cell, e.g. the induction of cytokines and reactive oxygen species, are functionally connected
with NF-κB. In the case of PBMCs treated both with PRP and NP simultaneously as well as
30 min before induction with LPS, 40% inhibition of NF-κB activity was observed. The
results obtained suggests that the inhibitory effects of PRP and its active nonapeptide could be
connected with the regulation of transcription processes.
Laboratory of Glycobiology
Head: Professor Maciej Ugorski, Ph.D., D.V.M.
Study on the structure and functions of cell adhesion molecules
Promoter analysis of the human α1,3/4-fucosyltransferase gene (FUT III)
In our previous studies we cloned and sequenced the promoter of human α1,3/4fucosyltransferase. The presence of three binding sites for AP-1 transcription factor in the
region representing the enhancer element of FUT III promoter suggested that this protein
complex could be involved in the regulation of FUT III gene expression. To address this
hypothesis, electrophoretic mobility assay (EMSA) was performed. It was found that
oligonucleotides containing the AP-1 binding sequence corresponding to the region –672 to –
710 from the translation initiation site in FUT III were bound by nuclear extracts from human
colon carcinoma CX-1.1 cells. This observation was further confirmed by competition
analysis with unlabeled oligonucleotides and antibody recognition assay with anti-AP-1
antibody directed against the N-terminus of human c-Jun p39. In the latter case, the band with
the slowest mobility was identified as AP-1 complex, based on the reaction with anti-c-Jun
antibody. However, it was not supershifted completely, suggesting that it could contain Ap-1
family proteins other than c-jun transcription factor.
The promoter activity of FUT III gene and FUT3 mRNA expression was analyzed in
colon carcinoma cell lines with different expression of sialyl Lea using the prFUT3/S and
prFUT3/L constructs. A strong correlation between luciferase activity and mRNA level and
the presence of the sialyl Lea was found in the analyzed cell lines. These results support
earlier data on the relations between the expression of FUT3 and the amount of this
carbohydrate structure.
DEPARTMENT OF MICROBIOLOGY
Head: Professor Jolanta Zakrzewska-Czerwińska, Ph.D.
Laboratory of the Molecular Biology of Microorganisms
Head: Professor Jolanta Zakrzewska-Czerwińska, Ph.D.
The molecular basis of replication and gene expression and the design of
compounds inhibiting these processes
Initiation of bacterial chromosome replication
Bacterial chromosome replication is mediated by a single initiator protein, DnaA, that
interacts specifically with multiple DnaA boxes located within the origin (oriC).
Streptomycetes are Gram-positive mycelial soil bacteria with unique cell division features;
they grow as substrate mycelia which differentiate to aerial mycelium and spores. The
compartments of vegetative hyphae contain several copies of uncondensed chromosomes
between occasional cross-walls, while the syncytial aerial hyphal tips may contain more than
50 copies of the chromosome. In Streptomyces coelicolor, replication is initiated by the DnaA
protein at the centrally located oriC region and proceeds bidirectionally until the replication
forks reach the ends of the linear chromosome. Most studies on the regulation of chromosome
replication have focused on unicellular rod-shaped bacteria (dividing by binary fission),
particularly on E. coli, with a single circular chromosome. The obvious differences between
these bacteria and filamentous Streptomyces containing elongated compartments with
multiple copies of a linear chromosome may imply differences in the regulation of
chromosome replication. We identified three clusters of DnaA boxes (H24, H69, and D78)
which lie within a relatively short segment of chromosome centered on the oriC region.
Among the analyzed clusters, D78 exhibits the highest affinity toward the DnaA protein; the
affinity of DnaA for the D78 cluster is about fivefold higher than that for oriC. The highaffinity DnaA boxes appear to be involved in the stringent control of chromosome replication
particularly during the maturation of aerial mycelium. Deletion of D78 causes more frequent
chromosome replication (an elevated ratio of origins to chromosome ends was observed) and
earlier colony maturation. In contrast, delivery of extra copies of D78 causes slow colony
growth, presumably as a consequence of a reduction in the initiation frequency of
chromosome replication. We speculate that the number of high-affinity DnaA boxes is
relatively constant within hyphal compartments and that the deletion of D78 therefore permits
an increased copy number of either the chromosomal origin region or a plasmid harboring the
D78 cluster.
Laboratory of Signaling Proteins
Head: Associate Professor Wojciech Gorczyca, Ph.D.
Studies on proteins involved in the activation of proinflammatory transcription
factors in immune cells
We have continued studies on the regulatory role of cGMP-dependent signaling pathways
in the activity of NF-κB and AP-1 in human peripheral blood mononuclear cells (PBMCs)
and in rat peritoneal macrophages (rPMs). In PBMCs the elevation of cGMP resulted in
activation of both transcription factors. This stimulatory effect of cGMP was additionally
supported by the observed increase in IL-6 and TNF-α expression. On the other hand, in
rPMs, which do not express cGMP-dependent protein kinase (PKG), induction of cGMP did
not influence the NF-κB activity, but caused an elevation in AP-1 activity. Taken together,
our results indicate that cGMP use different signaling pathways in the regulation of activity of
each transcription factor.
DEPARTMENT OF EXPERIMENTAL ONCOLOGY
Head: Associate Professor Adam Opolski, Ph.D.
Laboratory of Experimental Anticancer Therapy
Head: Associate Professor Adam Opolski, Ph.D.
Studies on the mechanisms of tumor progression and metastasis and the effects of
experimental antitumor therapy
Correlation between the VDR expression and antiproliferative activity of vitamin D3
compounds in combination with cytostatics
Calcitriol is a potent antiproliferative agent against various tumor cells in vitro. Its
biological activity is mediated by the vitamin D receptors (VDRs). Here we present the results
of study of vitamin D3 compounds (calcitriol and its analogue PRI-2191) as potential agents
in combined antitumor therapy in vitro. Applying anti-proliferative SRB and MTT assays, we
measured the growth inhibitory effects of vitamin D compounds applied alone or in
combination with either cisplatin or doxorubicin. Next we examined the correlation of this
effect with the presence of nVDR (nuclear VDR). The following cancer cell lines were
applied: HL-60 (human leukemia), SW707 (human colon cancer), A549 (human lung cancer),
and WEHI-3 (mouse leukemia). We have shown that the treatment of tumor cells with the
combination of vitamin D compounds and cytostatics decreased the 50% inhibitory
concentration (IC50) values compared with the effects of cytostatics applied alone. The
synergistic effect was positively correlated with nVDR expression.
Studies on the mechanisms of MC38 colon carcinoma growth inhibition as the effects of
experimental anti-tumor therapy with mouse dendritic cells (DCs) were continued
Our experiment proved that both the DCs of the JAWS II line loaded with lysate tumor
antigen (JAWS II/TAg) and those transduced with IL-12 gene (JAWS II/IL-12) were able to
migrate effectively to draining lymph nodes and activate immune response in vivo. The
optimal effect was visible when mice were treated with JAWS/IL-12 cells. On the seventh day
after vaccine administration, necrotic and apoptotic changes in tumor tissue as well as
infiltrating lymphocytes were observed. In addition, spleen cell cytotoxicity towards MC38
cells gradually increased up to the seventh day. Three or four injections of mice with JAWS
II/IL-12 cells, JAWS II/TAg, or both resulted in significant tumor growth inhibition. The
most effective was the administration of JAWS II/IL-12 + JAWS II/TAg cells, which resulted
in long-lasting, statistically significant tumor growth delay. Comparative studies on the antitumor effect of IL-12 or IL-2 transduced murine JAWS II cells vaccine were performed.
Percentage differences in cells expressing maturation markers after efficient transduction with
both SAMEN IL-12 and pQNIL-2 retroviral vectors were observed (CD86 down-regulation in
the case of JAWS II/IL-2 cells). Despite the effective transduction of the JAWS II/IL-2 cells,
no significant tumor delay was observed even if JAWS II/TAg+JAWS II/IL-2 cells were
applied for vaccination. The T cell activation ability and anti-tumor activity of IL-12transduced and tumor antigen-loaded mouse BM-DCs at different stages of maturation were
also investigated.
Moreover, we positively answered the question whether bacteriophages support antitumor response initiated by DC-based vaccine in murine transplantable colon carcinoma We
supposed that DC-phage interactions could intensify immune response in tumor-bearing mice.
This phenomenon may be of potential use in anti-cancer immunotherapy. In collaboration
with the Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic,
we conducted studies on the synergy of a CBM-4A ifosfamide derivative and IL-12 in mouse
HPV 16-associated TC-1 tumor therapy.
Laboratory of Biomedicinal Chemistry
Head: Associate Professor Janusz Boratyński, Ph.D., Eng.
Studies on the methotrexate – fibrinogen conjugates
The Laboratory of Biomedical Chemistry is focused on the development of drug-carrier
conjugates for the treatment of experimental cancer and immunological diseases. We
investigate the biochemical properties and biological activities of protein (fibrinogen,
albumin, antibodies) and carbohydrate (glucose or mannose polymers) methotrexate and
raltitrexed conjugates.
Physiochemical studies of bacteriophages
Beside the chemical modification of macromolecules, we are investigating the
physicochemical properties of bacterial viruses, or bacteriophages. In particular, we aim at
developing an effective procedure for the purification of bacterial viruses.
DEPARTMENT OF EXPERIMENTAL THERAPY
Head: Professor Michał Zimecki, Ph.D.
Laboratory of Immunopathology
Head: Professor Irena Frydecka, M.D.
The mechanisms of immune deficiency in neoplastic diseases and autoimmune
diseases
Recently, increased serum levels of the soluble form of CTLA-4 (sCTLA-4) generated by
alternatively spliced CTLA-4 mRNA have been reported in several autoimmune diseases.
This molecule is considered to be a new marker in these diseases. The purpose of the study
was to investigate serum levels of sCTLA-4 and the effect of ex vivo stimulation with antiCD3+rIL-2 on the production of sCTLA-4 by peripheral blood mononuclear cells (PBMCs) in
patients with multiple sclerosis (MS) compared with normal subjects. Studies were performed
in 37 patients with relapsing-remitting (RR) and 26 with the secondary progressive (SP) form
of disease and in 24 age- and sex-matched healthy subjects. The serum and culture
supernatant sCTLA-4 levels were estimated using ELISA (Bender, Germany). Patients with
RRMS had significantly higher levels of sCTLA-4 in sera than patients with SPMS (p=0.006)
and healthy controls (p=0.014). There was statistically higher production of sCTLA-4 by ex
vivo stimulated PBMCs in RRMS and SPMS patients compared with normal subjects
(p=0.001, p=0.001, respectively). In addition, spontaneous production of this molecule by
PBMCs was observed in RRMS and SPMS patients. The levels of this molecule in culture
supernatants were higher in RRMS patients (p=0.003) and SPMS (p=0.003) compared with
normal controls. This is the first report showing increased sCTLA-4 serum levels in patients
with RRMS and increased spontaneous and stimulated sCTLA-4 production by PBMCs in
both groups of MS patients. The biological significance of sCTLA-4 in MS is unclear and
requires further studies.
The pathogenesis of B-cell malignancies is poorly understood and associated with a
disturbance in immune regulation. The CTLA-4 molecule plays an important role in immune
regulation by downregulating the activation of T cells. Polymorphisms in the CTLA-4 gene
have been shown to be associated to a number of autoimmune diseases and
lymphoproliferative disorders (multiple myeloma, non-Hodgkin’s lymphoma). We analyzed
three intragenic polymorphisms at the CTLA-4 gene positions C-319T, A49G, and the
dinucleotide (AT)n repeat polymorphism at position 642 in exon 3 in patients with B-CLL
and in healthy controls. One hundred ten B-CLL patients and 105 healthy subjects were
studied. Genomic DNA was isolated from whole frozen blood using the NucleoSpinR Blood
kit (MARCHEREY-NAGEL, Germany). Allele identification was achieved by PCR
amplification. The amplified product for SNP loci was purified and minisequenced using the
commercial kit SnapShot (PE Applied Biosystems). The dinucleotide repeat polymorphism
was studied by PCR and the fluorescence-based technique. The products were analyzed on an
ABI PRISM 310 Genetic Analyzer (ABI PRISM 310 capillary electrophoresis system).
Genotype analysis showed that the T allele at position -319 in the promoter region was overrepresented among patients with B-CLL (P=0.0055, OR=2.10, 1.46<95%CI<2.91). No
difference was observed for the A49G and the (AT)n polymorphisms (P>0.05). The three
CTLA-4 gene polymorphism C-319T, A49G, and 642(AT)n are in tight linkage
disequilibrium with each other; therefore we extended the analysis to the haplotype
distribution. The haplotypes -319C+49A(AT)8 and -319C+49G(AT)>8 were the most common
both in patients and controls, with a frequency slightly higher in patients. No particular
haplotype was significantly over-represented in affected or in healthy individuals. These
findings indicate that the T allele at position -319 of the promoter region confers susceptibility
to B-CLL in the Polish population.
Laboratory of Immunobiology
Head: Professor Michał Zimecki, Ph.D.
Studies on the mechanism of action of synthetic and natural immunomodulators
of potential application in prevention and therapy
Studies on the adjuvant activity of the lactoferrin:monophosphoryl lipid A complex
(LF:MPL) were continued. We demonstrated its adjuvant activity in the induction of both
humoral as well as cellular immune response. An increase in specific antibody production was
shown in the case of ovalbumin and Plesiomonas shigelloides immunization. Immunization of
mice with Plesiomonas shigelloides together with LF:MPL complex protected the animals
against Plesiomonas-induced sepsis.
Studies regarding the involvement of respective regions in the lactoferrin molecule in its
immunotropic activities were also continued. For the in vivo and in vitro studies, native
bovine and human LFs as well as recombinant human LF of plant origin were used. Both the
native and recombinant LFs did not differ in their antigenic properties toward LF-specific
T-cell lines. On the other hand, recombinant LF exhibited significantly lower adjuvant
property than native LF. Since we had previously shown that the carbohydrate part of the LF
molecule was essential for the adjuvant effect of LF, we concluded that a different
composition of the glycan moiety in the recombinant LF (sugars typical for plant
glycoproteins) cannot be recognized by antigen-presenting cells.
Other studies on milk-derived proteins demonstrated that glycomacropeptide, a derivative
of kappa casein from bovine milk, exhibited protective activity in experimental endotoxemia
and bacteremia.
In the course of our investigations on the protective action of bacteriophages in mice, we
showed that oral administration of as few as 104 specific phage particles may be protective in
animals intravenously infected with lethal doses of bacteria. In addition, lower (103) numbers
of bacteriophages could act with LF in an additive manner in the clearance of bacteria from
the organs of infected mice.
In vitro experiments revealed, in turn, that preincubation of phagocytes (human
neutrophils or monocytes) with bacteriophages led to inhibition of phagocytosis, this process
being observed both with homologous as well as heterologous bacteriophages. These results
support earlier findings that bacteriophages can affect the metabolism of eucariotic cells. In
contrast, preincubation of bacteria with homologous, but not heterologous, bacteriophages
facilitated the phagocytosis, suggesting that specific opsonization of bacteria may be involved
in that phenomenon.
A new method of isolating precursor osteoblast cells from human peripheral blood and
determining their osteolytic activity was described. The cells could also be isolated from other
species, such as guinea pig, rat, mouse, rabbit, and bovine. The technique is based on the
determination of C-telopeptides, the degradation products of collagen from the bone during
the osteolytic process. Mononuclear cells from the peripheral blood (PBMCs) acquire the
osteolytic activity in the course of culture in vitamin D-containing medium in the presence of
a substrate, i.e. a bone plate. Integrin receptors, which appear on immature precursor
osteoblast cells derived from PBMCs, are responsible for this activity.
DEPARTMENT OF CANCER IMMUNOLOGY
Head: Professor Paweł Kisielow, Ph.D.
Laboratory of Transgenesis and Lymphocyte Biology
Head: Professor Paweł Kisielow, Ph.D.
NWC, a new evolutionarily conserved gene within RAG locus
Recently we have identified NWC, a new, evolutionarily conserved gene overlapping with
the RAG locus. NWC is ubiquitously expressed, but in lymphocytes is differently regulated
than in other cells. In developing lymphocytes it is dependent on the activity of RAG1
promoter and is transcribed together with RAG1 as a RAG1/NWC hybrid transcript, while in
non-lymphocytes it is dependent on NWC's own promoter located in the RAG2 intron, which
in lymphocytes is silent.
This year we have identified hybrid RAG1/NWC transcripts also in human and chicken
thymocytes, indicating that their discovery reveals a general, evolutionarily conserved
phenomenon. Interestingly, two of the human hybrid transcripts, like the mouse hybrid
transcripts, contain a novel 'RAG2 antisense' exon of a highly orthologous sequence.
Together, these observations suggest that hybrid transcripts may have important biological
functions.
In order to characterize factors responsible for the activation of the NWC promoter in nonlymphoid cells and its silencing in lymphoid cells, we identified the minimal NWC promoter.
We found that the shortest fragment sufficient to activate the transcription of a reporter gene
in DLR assay performed in non-lymphoid cells spanned the region from -119 to +125
nucleotides in relation to the non-hybrid NWC transcription start site. Sequence alignment of
the characterized minimal promoter with the corresponding genomic sequences identified in
other mammalian species (human, chimpanzee, rat, and dog) revealed the presence of two
highly conserved motifs. Mutational analysis revealed that these fragments are necessary for
the promoter activity. However, the NWC promoter fragments were also active in a DLR
assay performed in lymphoid cells, suggesting that lymphoid cell-specific repression of the
NWC promoter may result from the activity of a distal silencer and/or a factor repressing the
transcription on the chromatin level.
DEPARTMENT OF MEDICAL IMMUNOLOGY
Head: Professor Andrzej Górski, M.D.
Laboratory of Bacteriophages
Head: Professor Andrzej Górski, M.D.
Immunobiology of bacteriophages and their application in the treatment of
bacterial infections and their possible role in host defense and disease
Previously we observed binding of T4 phage to the membranes of cancer and normal
blood cells. We selected a mutant, HAP1, with enhanced affinity for melanoma cells. Both T4
and HAP1 markedly and significantly inhibited experimental lung metastasis of murine B16
melanoma, and HAP1 was more effective than T4. We also found a mutation in the hoc gene
that differentiates bacteriophage HAP1 and its parental strain T4: a non-sense type mutation
that precludes proper synthesis of gpHoc. In our present work we proceeded with
investigations of phage-eukaryotic cell interactions.
We compared the antitumor activities of bacteriophages after oral (per os) and
intraperitoneal (i.p.) administration of lysates and purified preparations. Our observations
indicate that per os application of a bacteriophage preparation is safer and at least as effective
as i.p. Bacteriophages applied per os were more effective in inhibiting metastasis formation.
These observations are of great importance in any consideration of possible therapeutic
applications of bacteriophages.
We showed that T4 phage diminishes the luminol-dependent chemiluminescence of
peripheral blood polymorphonuclear leukocytes stimulated by the lipopolysaccharide of
Escherichia coli. The effect was also observed when live bacteria were used for stimulation
and it was independent of the bacterial susceptibility to T4-mediated lysis. On the other hand,
T4 did not influence ROS formation by polymononuclear leukocytes stimulated by PMA.
These findings indicate that the elements of the mechanism enabling the phage to infect
bacteria may not be involved in the observed phenomenon and that it is specific to some
degree and may depend on the kind of activator. These observations provide new evidence for
possible interactions between phages and mammalian cells.
In the course of our studies on the application of olfactory ensheathing cells (OECs) in the
treatment of complete spinal cord injuries in humans, conducted in collaboration with the
Department of Neurosurgery of the Wroclaw Medical University, we showed that the
cadaver-derived olfactory bulb and olfactory mucosa can be considered a reliable source of
OECs. Efficient culture of OECs from the cadaver olfactory bulb was possible when the warm
ischemia time was less than 20 minutes. In contrast, OECs derived from cadaver olfactory
mucosa were resistant to warm ischemia lasting even 180 minutes. We also developed a
simple procedure for short-term storage (up to 14 days) and partial purification of OECs by
keeping them in nonadherent conditions. This enables grafting OECs without the necessity of
using additional procedures connected with cell culture and purification (e.g. enzymatic
detachment of cells, storage in liquid nitrogen).
Bacterial infections remain a major medical challenge in view of increasing antibiotic
resistance among different bacterial strains. Coagulase-negative staphylococci (CoNS) have
become the most often isolated bacteria from the blood cultures, spinal fluid, and respiratory
tracts of neonates. These nosocomial strains are often resistant to many different groups of
antibiotics. The sensitivity spectra of 50 CoNS strains isolated from neonatal bloodstream
infections to antibiotics and to 23 specific staphylococcal bacteriophages were determined.
Sixty percent of the multidrug-resistant staphylococci isolated from severe neonatal infections
were sensitive to four bacteriophages, but most of these isolates exhibited high rates of
resistance to vancomycin. The possible therapeutic use of phages was postulated.
Impact of specific bacteriophages on the properties of the sperm of boars infected by the
blue pus bacterium Pseudomonas aeruginosa
The aim of the observations was to assess the influence of specific bacteriophages on the
properties of the sperm of boars infected by the blue pus bacterium. The study covered 15
boar reproducers; 5 of them had been experimentally infected with Pseudomonas aeruginosa,
whereas the remaining 10 were males in use at the Pig Insemination Station in whose
preputial sac or sperm the microorganism concerned had been discovered. The therapy was
pursued for three weeks. Before and after the treatment, sexual responses, sperm (quantity,
concentration of spermatozoa, percentage of sperm cells having correct movement, their
morphology and survival rate), peripheral blood, and the capacity of blood cells to produce
cytokines were examined. No essential differences between the studied sexual responses
before and after the therapy were found. Of the sperm properties, the only statistically
significant differences were recorded for sperm cell survivability in the BTS dilutor, which
increases after the treatment by 230-242%. After the therapy with bacteriophages, a decline
was found in the level of IL-10 in blood serum and supernatants of cell cultures stimulated
with LPS and those unstimulated. The results obtained (improvement of the survivability of
spermatozoa) wholly justify the need to employ the bacteriophage therapy in the treatment of
reproductive boars infected by the blue pus bacterium.
Laboratory of Cellular Interactions
Head: Associate Professor Danuta Duś, Ph.D.
New markers of tumor progression. Cancer cell-endothelial cell interactions
during metastatic spread of cancer cells
The variable outcome of cancer patients with similar clinical status creates a need to
search for new and reliable prognostic indicators of tumor progression, recurrence, and
survival. The aim of the study was to determine the prognostic value of new molecular traits
of tumor cells in urinary bladder and breast cancer which could determine tumor progression
and metastatic growth. The prognostic value of flow cytometric evaluation of DNA ploidy
and tumor cell proliferative activity in surgical biopsies of kidney tumors were examined. In
renal cancer, aneuploidy in combination with T>2 clinical stage and the presence of a high
fraction of proliferating tumor cells indicated for increased probability of tumor progression.
Soluble intercellular adhesion molecule-1 (sICAM-1) level was examined in renal cancer
patients. It has been observed that preoperative high sICAM-1 level (<221 ng/ml) was
connected with a high probability of post-operative disease progression and metastatic tumor
growth. In breast cancer, the level of Fas/FasL expression in the tumor tissue of 130 patients
with stage II breast carcinoma was evaluated. The results, analyzed after five years' follow-up,
indicated that Fas presence on human breast cancer cells significantly correlated with the
lower rate of lymph node involvement, longer disease-free time, and survival.
Our studies on endothelial cells (ECs) are aimed at their phenotypic characteristics,
particularly their activation mechanisms and organ-specific adhesive interactions under
normal and pathological conditions. Natural killer (NK) cells are innate effector cells that
play a critical role in the early defense against viral infection and malignant transformation.
On the other hand, ECs are critical in the recruitment and migration of circulating effector
cells into sites of inflammation and necrosis. EC injury occurs in a variety of pathologic
infections, autoimmunity, transplantation, and graft-vs.-host disease and may result from
cytotoxicity toward ECs mediated by effector lymphocytes. We showed that organ-specific
NK-mediated EC killing occurs in an IL-2 activation-dependent manner. Human NK cells
were able to adhere and kill human endothelial cell cell lines. To decipher the way in which
NK cells are recruited and bind the endothelial layer to enter the tissue underneath, we
studied the adhesion mechanism of NK and ECs. Correlation was observed between the
adhesion pattern and the susceptibility to NKL2-mediated killing. To identify the cytotoxic
pathway used by NKL2 cells, the involvement of the classical and alternate pathways was
examined, indicating a predominant role of the perforin/granzyme pathway. The interaction
between NKL2 effectors and ECs induced cytochrome c release and Bid translocation in
target cells, indicating an involvement of the mitochondrial pathway in NKL2-induced EC
death. The present studies emphasize that human NK cell cytotoxicity toward ECs may be a
potential target to block vascular injury or, alternatively, to destroy the pathological vessels
involved in the development of invasive pathologies such as cancer.
Studies on endothelial cells were performed in collaboration with Dr. C. Kieda, CBM
CNRS UPR 4301, Orleans, France, and Dr. S. Chouaib, Institut Gustave Roussy,
INSERM U487, Villejuif, France.
Laboratory of Reproductive Immunology
Head: Associate Professor Anna Chełmońska-Soyta, V.D.
Immunological mechanisms associated with reproductive processes in health and
disease
Cytokines in endometriosis
Endometriosis, a common disease in women of reproductive age is characterized by the
presence of endometrial tissues outside the uterus. Dysmenorrhea, pelvic pain, and infertility
are the main clinical manifestation of the disease. An immunological basis has been
considered to be important in the pathogenesis of endometriosis. Chemokines are seen as one
of the most important factors in the development of endometriotic implants. The aim of the
study was to test the serum monocyte chemotactic protein level and to determine the
population of immune cells secreting this chemokine. In women with endometriosis there was
a significantly higher serum level of MCP-1 compared with healthy women and women with
leiomyoma. In women with adenomiosis and advanced endometriosis there was a
significantly higher number of CD14+ cells producing MCP-1 than in healthy women and
women with leiomyoma.
Male infertility
Fibronectin has been found in tissues and fluids of the male reproductive tract. It is a
component of spermatozoa, basement membrane of the testis, and epididymal and seminal
fluid. The exact role of fibronectin in ejaculated semen is not known. The aim of the study
was to identify degradation products of fibronectin in relation to the results of general semen
examination. The relative amounts of 60, 90, and 100 kDa FN fragments were 2-3 times
higher in seminal plasmas with abnormal semen characteristics than in a normozoospermic
group.
Laboratory of Virology
Head: Professor Zofia Błach-Olszewska, Ph.D.
Study on nonspecific immunity in viral infection
The innate antiviral immunity of leukocytes in patients with chronic renal failure on
hemodialysis was compared with that of a control group. The immunity was measured using
the method of direct infection of peripheral blood leukocytes with indicatory VS (vesicular
stomatitis) virus. The VS virus did not replicate in leukocytes with strong innate immunity,
whereas by impaired immunity the virus multiplied to high titer. Patients on hemodialysis
expressed the same levels of nonspecific antiviral immunity as the control group. This means
that antiviral immunity was not impaired in chronic hemodialysed patients.
The activity of leukocytes from the lower respiratory tract of patients with lung
inflammatory diseases with regard to coexisting viral or bacterial airway infections was
studied. Assessment of the local inflammatory response in bronchial asthma patients indicate
that the reduction in the activation of NFκB and the inhibition of production of TNFα and
IL-6, but not IFNα and IFNβ, in pulmonary leukocytes may be a consequence of inhaled
corticosteroid therapy. Analysis of the interrelationship between clinical status of the patients
and the production of pro-inflammatory and antiviral cytokines revealed that IFNγ, which was
produced only in the corticosteroid-treated patients, can involve, apart from IL-6 and TNFα,
in deterioration of clinical symptoms.
There is increasing evidence to support the role of immune mechanisms in the
pathogenesis and progression of chronic heart failure (CHF). Recent studies investigating
signaling pathways responsible for the activation of the pro-inflammatory cytokine system in
CHF revealed the role of nuclear factor kappa-B (NF-κB). The aim of study was therefore to
evaluate the pattern of activation of the NF-κB system in peripheral blood leukocytes (PBLs)
from CHF patients according to the severity and etiology of CHF and to relate it to clinical
status, exercise intolerance, and inflammatory status. Additionally, in a series of in vitro
experiments, the role of LPS as a stimulus for the NF-κB system in PBLs was evaluated.
There is some evidence that in CHF patients, elevated LPS levels in peripheral blood can be a
strong immune activator through action on circulating immunocompetent cells, with
downstream activation of the NF-κB system as a signal transducer of immune response to
LPS.
Laboratory of Tissue Immunology
Acting head: Assistant Professor Beata Nowakowska, Ph.D.
The rare allele HLA locus B in the south-west Polish population
We continued the investigation on population genetic of HLA system. The aim of our
study was to verify, by typing at the DNA level, the frequencies of the rare allele HLA locus
B. A total of 325 unrelated, healthy individuals of both sexes living in the Wrocław area and
in the neighboring districts were included in the study. Of the rare alleles we typed B*1503
(B72), B*1509 (B70), and B*1510 (B70) with a frequency of 0.006. We observed in our
population the very rare alleles B*42 (recombinant B*07 and B*08) , B*54, and B*67 with a
frequency of 0.0006
The HLA B*48, B*46, B*59, and B*53 alleles were not found in our study, although they
are present in other caucasoid populations.
Genetic predisposition to cancer development
A polymorphism of p53 at codon 72 encoding an arginine (arg) or proline (pro) residue is
located in a proline-rich region of p53 protein, a domain important for growth suppression and
apoptosis. The two p53 variants have been reported to have different biochemical and
functional properties. However, the significance of this polymorphism in respect to cancer
risk is still uncertain. Strong correlation between the p53 codon 72 polymorphism and
ethnicity is well known, and the arg allele is prevalent in populations living further away from
the Equator. It is possible that the phenomenon of uneven allele distribution is further
complicated by a differential allele expression in heterozygotes. We evaluated the expression
status of codon 72 polymorphic alleles in healthy Polish (Caucasian) and Chinese (Asian)
populations (collaboration with Dr K. Sabapathy, Laboratory of Molecular Carcinogenesis,
National Cancer Center, Singapore) and in cancer patients. Preferential expression of the arg
allele in healthy Polish heterozygote (arg/pro) subjects and the pro allele in Chinese
heterozygotes (arg/pro) was observed. However, in the normal tissue surrounding the breast
tumors of Chinese cancer patients, expression of the arginine instead of proline polymorph
was observed. In the Polish patients, mostly with hematological neoplasms, the arginine
polymorph seemed to be the preferentially expressed allele. The data point to the codon 72
expression status as a potential marker of an increased risk of cancer.
Genetic polymorphisms and ovarian cancer
Variations in DNA sequences may explain some of interindividual differences in druginduced adverse reactions and therapeutic responses. Among the genes which potentially may
have an impact on patient response to chemotherapy are genes coding for drug-metabolizing
enzymes, ABC transporters affecting both drug biodistibution and cancer sensitivity to
chemotherapy, and members of DNA-repair pathways which might also influence cancer
sensitivity to cytostatic agents. In a case-control study we investigated several singlenucleotide polymorphisms (SNP) in genes of the above-mentioned classes. In general, the
frequencies of the studied variant alleles were similar in ovarian cancer patients and in the
control group.
DEPARTMENT OF CLINICAL IMMUNOLOGY
Head: Professor Andrzej Lange, M.D.
Laboratory of Immunogenetics
Head: Associate Professor Piotr Kuśnierczyk, Ph.D.
CTLA-4 gene polymorphism in allergic asthma
The cell surface receptor CTLA-4 is an important negative regulator of T cell activation.
We hypothesized that polymorphisms of the CTLA-4 gene influencing the gene expression,
mRNA stability, or the intracellular transport of the CTLA-4 molecule may contribute to
allergic asthma. Three single-nucleotide polymorphisms, -1147 C/T and -318 C/T in the
promoter region and +49 A/G, which changes an amino acid in the leader peptide which
affects the intracellular transport of the protein, and a microsatellite 642 (AT)n in the 3’untranslated region, influencing mRNA stability, were tested. No statistically significant
differences between patients and controls in any of these polymorphisms were found.
CTLA-4 gene polymorphisms and soluble CTLA-4 peripheral blood levels in psoriasis
vulgaris
Psoriasis vulgaris is one of most frequent skin diseases in our population. It is an
autoimmune disease of unknown etiology. We compared the frequencies of four CTLA-4
polymorphisms: -1147 C/ T, -318 C/T, +49, and 642 (AT)n, in 116 patients with psoriasis
vulgaris and 123 healthy donors. No statistically significant differences were found between
the groups. However, levels of soluble CTLA-4 were significantly (p=0.022) higher in
patients than in controls, and the difference was even more prominent (p=0.0055) for type I
psoriasis (age at onset below 41 years). This result suggests that soluble CTLA-4 may be
involved in the regulation of autoimmunity in psoriasis.
DEPARTMENT OF INFECTIOUS DISEASE MICROBIOLOGY
Head: Professor Andrzej Gamian, Ph.D.
Laboratory of Medical Microbiology
Head: Professor Andrzej Gamian, Ph.D.
Studies on the pathogenesis of some diseases of bacterial etiology and a role of
bacterial surface glycoconjugates and protein antigens in immune response
Current activity of this laboratory is focused on studies of the mechanisms of
pathogenicity of diseases with bacterial etiology, the role of molecular mimicry, bacterial
proteins, and glycolipids in pathogenicity, and the structure and functions of bacterial
capsular antigens and endotoxins. In the search for molecular markers of bacterial infections
and prognostic factors, a method for the determination of endotoxins was elaborated (J.
Microbiol. Meth., 2006, 64, 171-184). The method relies on the determination of a chemical
marker of endotoxin, 2-keto-3-deoxy-octulosonic acid, using GLC-MS (Kdo method). The
specificity of the method covers a broad spectrum of endotoxins due to the enzymatic
dephosphorylation of the interfering phosphate substituent of Kdo. The monitoring of
specific markers for sepsis and septic shock could significantly facilitate the prognosis of
these diseases and their treatment. Consequently, the second approach relies on the detection
of another marker of endotoxin, 3-hydroxy fatty acids, which allow measurement of its level
in patient sera (Arch. Immunol. Ther. Exp., 2005, in press). The general strategy for the
elaboration of the protective tools against invading bacteria comprise the determination of the
structures of the molecules involved in an infection and immune processes, their chemical
and genetic manipulations, as well as understanding their biological activities. The
interference of some bacterial components with functions of tissue structures may contribute
to the mechanisms of pathogenicity. Due to structural mimicry, care should be taken when
antibacterial vaccines are constructed to avoid the induction of autoantibodies. In this area we
have identified an enolase-like 45-kDa outer-membrane protein which mimics human muscle
enolase (FEMS Immunol. Med. Microbiol., 2005, 45, 53-62). Such a protein may be involved
in pathogenicity. Another bacterial protein was found to be a useful carrier for safe and
effective vaccines, namely fimbria (FEMS Immunol. Med. Microbiol., 2005, 45, 221-230).
Publikacje - 2005
Prace opublikowane w czasopismach znajdujących się na liście filadelfijskiej
1. Artym J., Zimecki M., Kuryszko J., Kruzel M.: Lactoferrin accelerates reconstitution of
the humoral and cellular immune response during chemotherapy-induced immunosuppression and bone marrow transplant in mice. Stem Cells Develop., 2005, 5, 548-555
IF – 2,11
2. Badowska-Rosłonek K., Kaczmarek L., Ramza J., Godlewska J., Opolski A., PeczynskaCzoch W.: New glycoside derivatives of 6H-indolo[2,3-b]quinolines. Pol. J. Chem.,
2005, 79, 369-386 IF – 0,640
3. Bernardini D., Nasulewicz A., Mazur A., Maier J.A.M.: Magnesium and microvascular
endothelial cells: a role in inflammation and angiogenesis. Front. Biosci., 2005, 10,11771182 IF – 3,226
4. Bielawska-Pohl A., Crola C., Caignard A., Gaudin C., Duś D., Kieda C., Chouaib S.:
Human natural killer cells kill organ-specific endothelial cells: analysis of the adhesion
and cytotoxic mechanisms. J. Immunol., 2005, 174(9), 5573-82 IF – 6,486
5. Błach-Olszewska Z., Zaczyńska E., Kiełbiński M., Frydecka I.: Deficiency of innate
immunity of leukocytes is associated with the failure of the induction of remission and
survival time in patients with acute leukemia. Pol. J. Envir. Stud., 2005, 14, Suppl. II,
36-40 IF - 0,639
6. Błach-Olszewska Z.: Innate immunity: cells, receptors and signaling pathways. Arch.
Immunol. Ther. Exp., 2005, 53, 245-253 IF – 0, 0663
7. Bogunia-Kubik K., Lange A.: HSP70-hom gene polymorphism in allogeneic
haematopoietic stem cell transplant recipients correlates with the development of aGvHD.
Transplantation, 2005, 79(7), 815-820 IF – 3,568
8. Bogunia-Kubik K., Młynarczewska A., Wysoczańska B., Lange A.: Recipient interferongamma 3/3 genotype contributes to the development of chronic graft-versus-host disease
after allogeneic hematopoietic stem cell transplantation. Haematologica, 2005, 90(3),
425-426 IF - 4,192
9. Cebrat M., MiąŜek A., Kisielow P.: Identification of a third evolutionarily conserved gene
within RAG locus and its RAG1-dependent and -independent regulation. Eur. J. Immunol.
2005, 35, 2230-2238 IF – 5,005
10. Cembrzyńska-Nowak M., Liebhart J., Bieńkowska-Haba M., Liebhart E., Kulczak A.,
Siemieniec I., Dobek R., Dor A., Barg W., Panaszek B.: The overproduction of nitric
oxide associated with neutrophil predominance is relevant to airway mycotic infections in
asthmatics undergoing prolonged glucocorticoid treatment. Cell. Mol. Biol. Lett., 2005;
10, 677-687 IF – 0,495
11. Chrobak A., Radzikowski C., Opolski A.: Side-chain-modified analogs of calcitriol cause
resistance of human HL-60 promyelocytic leukemia cells to drug-induced apptosis.
Steroids, 2005, 70, 19-27 IF – 2,337
12. Cisowska A., Bugla-Płoskońska G., Gamian A., Doroszkiewicz W., Jankowski S.:
Relationship between succeptibility to bactericidal action of serum and outer membrane
protein patterns in E. coli K1 strains. Pol. J. Environm. Studies, 2005, 14, suppl. II, 476482 IF –0,366
13. Crawley Ch., Szydlo R., Lalancette M., Bacigalupo A., Lange A., Brune M., Juliusson G.,
Nagler A., Gratwohl A., Passweg J., Komarnicki M., Vitek A., Mayer J., Zander A.,
Sierra J., Rambaldi A., Ringden O., Niederwieser D., Apperley J.F.: Outcomes of reduced
intensity transplantation for chronic myeloid leukaemia: an analysis of prognostic factors
from the Chronic Leukemia Working Party of the EBMT. Blood, 2005, 106: 2969-2976
IF - 9,782
14. Dąbrowska A., Baczyńska D., Widerak K., Laskowska A., Ugorski M.: Promoter analysis
of the human α1,3/4-fucosyltransferase gene (FUT III). Biochim. Biophys. Acta, 2005,
1731, 66–73 IF - 2,045
15. Dąbrowska K., Świtała-Jeleń K., Opolski A.., Weber-Dąbrowska B., Górski A.:
Bacteriophage penetration in vertebrates. J. Appl. Microbiol., 2005, 98, 7-13 IF – 1,835
16. Dąbrowska K., Opolski A., Wietrzyk J., Nevozhay D., Szczaurska K., Świtała-Jeleń K.,
Górski A.: Activity of bacteriophages in murine tumour models depends on the route of
phage administration. Oncol. Res., 2005, 15, 183-187 IF – 1,844
17. Dąbrowska K., Zembala M., Boratyński J., Kujawa A., Świtała-Jeleń K., Wietrzyk J.,
Opolski A., Górski A.: Bacteriophage HAP1: Molecular basis of its antitumour activity.
Clin. Immunol., 2005, 115 suppl. 1 177-178 IF – 3,034
18. Duk M., Kuśnierz-Alejska G., Korchagina EY., Bovin NV., Bochenek S., Lisowska E.:
Anti-alpha-galactosyl antibodies recognizing epitopes terminating with alpha 1,4-linked
galactose: human natural and mouse monoclonal anti-NOR and anti-P1 antibodies.
Glycobiology 2005, 15, 109-118 IF – 4,102
19. Feillet-Coudray C., Nasulewicz A., Jaffrelo L., Thien S., Coudray C., Rambeau M.,
Gueux E., Rayssiguier Y., Opolski A., Wolf F.I., Mazur A.: Erythrocyte magnesium
influx and efflux in solid tumour-bearing mice. Magnesium Res., 2005 18, 103-8 IF –
0,758
20. Fernando R., Szponar B., Sánchez A., Larsson L., Valero-Guillén P.L.: 3-Hydroxy fatty
acids in saliva as diagnostic markers in chronic periodontitis. J. Microbiol. Meth., 2005,
62, 285-291 IF – 2,146
21. Gmyrek G. B., Sozański R., Jerzak M., Chrobak A., Wickiewicz D., Skupnik A.,
Sieradzka U., Fortuna W., Gabryś M., Chełmońska-Soyta A.: Evaluation of monocyte
chemotactic protein-1 levels in peripheral blood of infertile women with endometriosis.
Eur. J. Obstet. Gynecol. Reprod. Biol., 2005, 122, 199-205 IF – 0,955
22. Godlewska J., Luniewski W., Zagrodzki B., Kaczmarek L., Bielawska-Pohl A., Duś D.,
Wietrzyk J., Opolski A., Siwko M., Jaromin A., Jakubiak A., Kozubek A., PeczyńskaCzoch W.: Biological evaluation of omega-(dialkylamino)alkyl derivatives of 6Hindolo[2,3-b]quinoline-novel cytotoxic DNA topoisomerase II inhibitors. Anticancer Res.,
2005, 25, 2857-2868 IF – 1,347
23. Gorczyńska E., Turkiewicz D., Rybka K., Toporski J., Kałwak K., Dyla A., Szczyra Z.,
Chybicka A.: Incidence, clinical outcome, and management of virus-induced hemorrhagic
cystitis in children and adolescents after allogeneic hematopoietic cell transplantation.
Biol. Blood Marrow Transplant., 2005, 11, 797-804 IF – 3,278
24. Gorski A.: The ethics of intellectual property rights in biomedicine and biotechnology: an
introduction. Sci. Eng. Ethics, 2005,11(1), 4-6 IF – 0,374
25. Górski A., Weber-Dąbrowska B.: The potential role of endogenous bacteriophages in
controlling invading pathogens. Cell. Mol. Life Sci., 2005, 62, 511-519 IF-4,812
26. Halary F., Pitard V., Dłubek D., Krzysiek R., de la Salle H., Merville P., Dromer C.,
Emilie D., Moreau J.-F., Dechanet-Merville J.: Shared reactivity of Vδneg γδ T cells
against cytomegalovirus-infected cells and tumor intestinal epithelial cells. J. Exp. Med.,
2005, 201(10), 1567-1578 IF - 14,588
27. Jakimowicz D., Gust B., Zakrzewska-Czerwińska J., Chater K.F.: Developmental-stagespecific assembly of ParB complexes in Streptomyces coelicolor hyphae. J. Bacteriol.,
2005, 187, 3572-3580 IF – 4,146
28. Jakimowicz P., Cheesman M.R., Bishai W.R., Chater K.F., Thomson A.J., Buttner M.J.:
Evidence that the Streptomyces developmental protein WhiD, a member of the WhiB
family, binds a [4FE-4S] cluster. J. Biol. Chem., 2005, 280, 9309-9315 IF–6,355
29. Jankowska E.A., von Haehling S., Czarny A., Zaczyńska E., Kuś A., Anker S.D.,
Banasiak W., Ponikowski P.: Activation of the NF-κB system in peripheral blood
leukocytes from patients with chronic heart failure. Eur. J. Heart Fail, 2005, 7, 984-990
IF – 2,938
30. Jaśkiewicz E., Jedynak A., Zioło E.: Expression of recombinant forms of human 21.5 kDa
myelin basic protein and proteolipid protein in CHO cells. Acta Biochim. Pol. 2005, 52,
863-866 IF – 1,03
31. Jasztold-Howorko R., Pelczynska M., Nasulewicz A., Wietrzyk J., Opolski A.: Synthesis
of 5,6-dimethyl-9-methoxy-1-phenyl-6H-pyrido[4,3-b]carbazole derivatives and their
cytotoxic activity. Arch. Pharm. (Weinheim), 2005, 338(11), 556-561 IF–0,653
32. Jerzak M., Chrobak A., Jakiel G., Baranowski W.: Annexin-V concentration in peritoneal
fluid of infertile women. Pol. J. Environ. Stud., 2005;14(Suppl. II), 561-563 IF – 0,639
33. Jerzykiewicz L.B., Lis T., Zuziak E.: X-ray structure of the dipotassium salt of
D-mannose 1-phosphate 3.25 hydrate. Carbohydr. Res., 2005, 340, 2422-2427 IF – 1,451
34. Kacprzak-Bergman I., Nowakowska B.: Influence of genetic factors on the susceptibility
to HBV infection, its clinical pictures and responsibility to HBV vaccination. Arch.
Immunol. Ther. Exper., 2005, 53, 139-142 IF – 0,663
35. Kalas W., Klement P., Rak J.: Downregulation of the angiogenesis inhibitor
thrombospondin 1 in fibroblasts exposed to platelets and their related phospholipids.
Biochem. Biophys. Res. Co., 2005, 334, 549-54IF – 2,83
36. Kalas W., Yu J.L., Milsom C., Rosenfeld J., Benezra R., Bornstein P., Rak J.: Oncogenes
and Angiogenesis: down-regulation of thrombospondin-1 in normal fibroblasts exposed to
factors from cancer cells harboring mutant ras. Cancer Res. 2005, 65, 8878-86. IF - 8,64
37. Kanska U., Salah Omar M., Budzynska R., Nevozhay D., Jagiello M., Opolski A.,
Boratynski J.: Antileukemic activity of glycated fibrinogen-methotrexate conjugates.
Anticancer Res., 2005, 25, 2229-2234 IF - 1,395
38. Karabon L., Wysoczańska B., Bogunia-Kubik K., Suchnicki K., Lange A.: IL-6 and IL-10
promoter gene polymorphisms of patients and donors of allogeneic sibling haematopoietic
stem cell transplants associate with the risk of acute graft-versus-host disease. Human
Immunol., 2005, 66(6), 700-709 IF - 2,664
39. Katzenellenbogen E., Kocharova N.A., Zatonsky G.V., Shashkov A.S., KorzeniowskaKowal A., Gamian A., Bogulska M., Knirel Y.A.: Structure of the O-polysaccharide of
Hafnia alvei strain PCM 1189 that has hexa- to octa-saccharide repeating units owing to
incomplete glucosylation. Carbohydr. Res., 2005, 340, 263-270 IF – 1,451
40. Katzenellenbogen E., Kocharova N.A., Zatonsky G.V., Shashkov A.S., Bogulska M.,
Knirel Y.A..:Structures of the biological repeating units in the O-chain polysaccharides of
Hafnia alvei strains having a typical lipopolysaccharide outer core region. FEMS
Immunol. Med. Mic., 2005, 45, 269-278 IF – 1,814
41. Kątnik-Prastowska I., Przybysz M., Chełmońska-Soyta A.: Fibronectin fragments in
human seminal plasma. Acta Biochim. Pol., 2005; 52, 557-560 IF – 1,032
42. Kisiela D., Kuczkowski M., Kiczak L., Wieliczko A., Ugorski M.: Differentiation of
Salmonella Gallinarum biovar Gallinarum from Salmonella Gallinarum biovar pullorum
by PCR-RFLP of the fimH gene. J. Vet. Med. B 2005, 52, 214–218 IF - 1,182
43. Kisiela D., Sapeta A., Kuczkowski M., Stefaniak T., Wieliczko A., Ugorski M.:
Characterization of FimH adhesins expressed by Salmonella enterica serovar Gallinarum
biovars Gallinarum and Pullorum: reconstitution of mannose-binding properties by single
amino-acid substitution. Infect. Immun. 2005, 73, 6187-6190 IF - 4,039
44. Kłopotowska D., Matuszyk J., Rapak A., Gidzińska B., Cebrat M., Zioło E., Strządała L.:
Transactivation activity of Nur77 discriminates between Ca2+ and cAMP signals.
Neurochem. Int. 2005, 46, 305-312 IF – 3,211
45. Kochanowska I.E., Niemira K., Wlodarski K., Liberek I., Ostrowski K.: Osteoinductive
properties of urothelium depend on bone morphogenetic proteins (BMP) inherency. Med.
Sci. Monitor 2005, 11(4), BR116-BR120 IF – 0,400
46. Kochel I., Rapak A., Zioło E., Strządała L.: Nur77 nuclear import and its NBRE-binding
activity in thymic lymphoma cells are regulated by different mechanisms sensitive to
FK506 or HA1004. Biochem. Biophys. Res. Co., 2005, 334, 1102-1106 IF – 2,83
47. Kosmaczewska A., Ciszak L., Suwalska K., Wołowiec D., Frydecka I.: CTLA-4
overexpression in CD19+/CD5+ cells correlates with the level of cell cycle regulators and
disease progression in B-CLL patients. Leukemia, 2005, 19, 301-304 IF – 5,81
48. Kovala-Demertzi D., Dokorou V.N., Jasinski J.P., Opolski A., Wiecek J., Zervou M.,
Demertzis M.A.: Organotin .ufenamates: Synthesis, characterization and antiproliferative
activity of organotin .ufenamates. J. Organomet. Chem., 2005, 690, 1800–1806 IF – 1,905
49. Kral T., Widerak K., Langner M., Hof M.: Propidium iodide and PicoGreen as dyes for
the DNA fluorescence correlation spectroscopy measurements. J. Fluorescence, 2005, 15,
179 – 183 IF - 1,195
50. Krawczenko A., Ciszak L., Malicka-Błaszkiewicz M.: Carp liver DNase – isolation,
further characterization and interaction with endogenous actin. Comp. Biochem. Phys.,
Part B, 2005, 140 (1), 141-151 IF – 1,393
51. Krawczenko A., Kieda C., Duś D.: The biological role and potential therapeutic application of interleukin 7 (IL-7). Arch.Immunol.Ther.Exp., 2005,53, 518-525 IF - 0,663
52. Kryczek I., Lange A., Mottram P., Alvarez X., Cheng P., Hogan M., Moons L., Wei S.,
Zou L., Machelon V., Emilie D., Terrassa M., Lackner A., Curiel T.J, Carmeliet P., Zou
W.: CXCL12 and vascular endothelial growth factor synergistically induce
neoangiogenesis in human ovarian cancers. Cancer Res., 2005, 65(2), 465-472 IF - 7,69
53. Kubis A., Marcinkowska E., Janusz M., Lisowski J.: Studies on the mechanism of action
of a proline-rich polypeptide complex (PRP): Effect on the stage of cell differentiation.
Peptides, 2005, 26, 2188–2192 IF – 2, 511
54. Kőbler-Kielb J., Pozsgay V.: Synthesis of neoglycoproteins by chemoselective ligation
through an aminoxy-thiol heterobifunctional reagent. J. Org. Chem. 2005, 70, 6987-6990
IF –3,462
55. Lipnicka U., Regiec A., Sulkowski E., Zimecki M.: New amides of 5-acyloamino-3methyl-4-isothiazolecarboxylic acid and their immunotropic activity. Arch Pharm
(Weinheim), 2005, 338(7), 322-328 IF – 0,653
56. Łakomska I., Golankiewicz B., Wietrzyk J., Pełczyńska M., Nasulewicz A., Opolski A.,
Sitkowski J., Kozerski L., Szłyk E.: Synthesis, spectroscopical characterization and the
biological activity in vitro of new platinum(II) complexes with imidazo[1,5-a]-1,3,5triazine derivatives and dimethylsulfoxide. Inorg. Chim. Acta, 2005, 358, 1911–1917 IF –
1,554
57. Mamczur P., Rakus D., Gizak A., Duś D., DŜugaj A.: The effect of calcium ions on
subcellular localization of aldolase-FBPase complex in skeletal muscle. FEBS Lett., 2005,
579, 1607-12 IF – 3,843
58. Mazur G., Bogunia-Kubik K., Wróbel T., Karabon L., Polak M., Kuliczkowski K., Lange
A.: IL-6 and IL-10 promoter gene polymorphisms do not associate with the susceptibility
for multiple myeloma. Immunol. Lett., 2005, 96(2), 241-246 IF - 2, 136
59. Mączyński M., Zimecki M., Drozd-Szczygieł E., Ryng S.: Synthesis, physicochemical
properties and immunological activity of 5-amino-3-methylisoxasolo [5,4-d] 4pyrimidone derivatives. Cell. Mol. Biol. Lett., 2005, 10, 613-623 IF – 0,495
60. Międzybrodzki R., Fortuna W., Weber-Dąbrowska B., Górski A.: Bacterial viruses against
viruses pathogenic for man? Virus Res., 2005, 110, 1-8 IF – 2,155
61. Nawrocka W., Sztuba B., Liszkiewicz H., Kowalska M.W., Wietrzyk J., Nevozhay D.,
Opolski A.: Synthesis and antiproliferative activity in vitro of new 2-aminobenzimidazole
derivatives. Part 2. Pol. J. Chem., 2005, 79, 709-716 IF – 0,640
62. Niedziela T., Letowska I., Lukasiewicz J., Kaszowska M., Czarnecka A., Kenne L.,
Lugowski C.: Epitope of the vaccine-type bordetella pertussis strain 186 lipooligosaccharide and antiendotoxin activity of antibodies directed against the terminal pentasaccharide-tetanus toxoid conjugate. Infect. Immun., 2005, 73, 7381-7389 IF–4,033
63. Nieva C., Gwoźdź T., Dutko-Gwoźdź J., Wiedenmann J., Spindler-Barth M., Wieczorek
E., Doliwa-Dobrucki J., Duś D., Henrich V., OŜyhar A., Spindler K-D. Ultraspiracle
(USP) promotes nuclear localization of ecdysteroid receptor (EcR) in mammalian cells.
Biol. Chem., 2005, 386(5), 463-70 IF – 3,598
64. Novik G.I., Astapovich N.I., Grzegorzewicz A., Gamian A.: Isolation and comparative
analysis of glycolipids from bifidobacteria. Microbiology, 2005, 74, (6), 670-677 IF –
0,539
65. Novik G.I., Astapovich N.I., Paściak M., Gamian A.: Biological activity of polar lipids
from bifidobacteria. Microbiology, 2005, 74 (6), 676-683 IF – 0,539
66. Pawlak E., Bilińska M., Suwalska K., Tutak A., Kosmaczewska A., Ciszak L., Frydecka
I.: Serum soluble CTLA-4 (sCTLA-4) levels in patients with multiple sclerosis. Pol. J.
Envir. Stud., 2005, 14, Suppl. II, 665-668 IF = 0,639
67. Pawlak E., Kochanowska I., Frydecka I., Bilińska M.: The soluble CTLA- receptor: a new
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68. Pelczynska M., Wietrzyk .J, Jaroszewicz I., Nevozhay D., Switalska M., Kutner A., Zabel
M., Opolski A.: Correlation between VDR expression and antiproliferative activity of
Vitamin D3 compounds in combination with cytostatics. Anticancer Res., 2005, 25, 22352240 IF - 1,395
69. Pozsgay V., Kőbler-Kielb J., Coxon B., Ekborg G.: Synthesis of glycolipid antigens of the
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70. Rostkowska-Nadolska B., Fortuna W., Szymaniec S., Międzybrodzki R.: The influence of
anti-inflammantory drugs on the proliferation of fibroblast derived from nasal polyps.
Auris Nasus Larynx. 2005, 32, 225-229 IF – 0,457
71. Rybka J., Gamian A.: Determination of endotoxin by the measurement of the acetylated
metyl glycoside derivative of Kdo with gas-liquid chromatography-mass spectrometry. J.
Microbiol. Meth., 2005, 64, 171-184 IF – 2,146
72. Ryng S., Zimecki M., Mączyński M.., Chodaczek G., Kocięba M.: Immunosuppressory
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73. Sebastian A., Szponar B., Larsson L.: Characterization of the microbial community in
indoor environments by chemical marker analysis: an update and critical evaluation.
Indoor Air, 2005, 15, Suppl. 9, 20-26 IF – 1,895
74. Siddique M.M., Balram C., Fiszer-Maliszewska, Ł., Aggarwal A., Tan A., Tan P., Soo
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implications in cancer development. Cancer Epidemiol. Biomarkers Prev.,2005, 14(9),
2245-52 IF – 4,72
75. Siemion I.Z., Gawłowska M., Ślepokura K. Biernat M., Wieczorek Z.: The mimetics of
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2005, 26, 1543-1549 IF – 2,511
76. Staniszewska M., Jarosz S., Jon M., Gamian A.: Advanced glycation end-products
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formed in the dry reaction at high temperature. Arch. Immunol. Ther. Exp., 2005, 53 (1),
71-78 IF – 0,663
77. Staniszewska M., Leszek J., Małyszczak K., Gamian A.: Are advanced glycation endproducts specific biomarkers for Alzheimer’s disease? Int. J Geriatr. Psychiatry, 2005,
20, 896-897 IF – 1,948
78. Staniszewska M., Nagaraj R.H.: 3-hydroxykynurenine-mediated modification of human
lens proteins: structure determination of a major modification using a monoclonal
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79. Szyda A., Pajtasz-Piasecka E., Krawczenko A., Grabarczyk P., Wysocki P., Koźlak J.,
Paprocka M., Mackiewicz A., Duś D.: Mouse colon carcinoma MC38 cell line for rapie
and accurate titration of amphotropic retroviral vector. Pol. J. Environ. Stud.; 2005, 14
(supp II) 790-794 IF – 0,366
80. Wąsowska M., Oszczapowicz I., Wietrzyk J., Opolski A., Madej J., Dzimira S.,
Oszczapowicz J.: Influence of the structure of new anthracycline antibiotics on their
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81. Wei S., Kryczek I., Zou L., Daniel B., Cheng P., Mottram P., Curiel T., Lange A., Zou
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carcinoma. Cancer Res., 2005, 65 (12), 5020-5026 IF – 7,69
82. Wesołowska O., Paprocka M., Koźlak J., Motohashi N., Duś D., Michalak K.: Human
sarcoma cell lines MES-SA and MES-SA/Dx5 as a model for multidrug resistance
modulators screening. Anticancer Res. 2005, 25, 383-9 IF –1,347
83. Wietrzyk J., Grynkiewicz G., Opolski A.: Phytoestrogens in cancer prevention and
therapy – mechanisms of their biological activity. Anticancer Res., 2005, 25(3), 23572366 IF - 1,395
84. Witkowska D., Mieszała M., Gamian A., Staniszewska M., Czarny A., PrzondoMordarska A., Jaquinod M., Forest E.: Major structural proteins of type 1 and type 3
Klebsiella fimbriae are effective protein carriers and immunogens in conjugates as as
revealed from their immunochemical characterization. FEMS Immunol. Med. Microbiol.,
2005, 45, 221-230 IF – 1,814
85. Witkowska D., Pietkiewicz J., Szostko B., Danielewicz R., Masłowski L., Gamian A.:
Antibodies against human muscle enolase recognize a 45-kDa bacterial cell wall outer
membrane enolase-like protein. FEMS Immunol. Med. Microbiol., 2005, 45, 53-62
IF – 1,814
86. Zabłocka A., Janusz M., Macała J., Lisowski J.: A proline-rich polypeptide complex and
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2005, 125, 35–39 IF – 2,531
87. Zaczyńska E., Magott-Procelewska M., Rybka K., Siemieniec I., Błach-Olszewska Z.,
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hemodialysis. Nephron Clin. Pract., 2005, 101, 207-210 IF – 0,878
88. Zawilak-Pawlik A., Kois A., Majka J., Jakimowicz D., Smulczyk-Krawczyszyn A.,
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complexes: orisomes from four unrelated bacteria. Biochem. J., 2005, 389, 471-481 IF –
4,278
89. Zimecki M., Artym J., Chodaczek G., Kocieba M., Kruzel M.: Effects of lactoferrin on the
immune response modified by the immobilization stress. Pharm. Rep., 2005, 57, 811-817
IF – 0,947
Wykaz publikacji opublikowanych w czasopismach polskich i innych zagranicznych:
1. Artym J., Zimecki M.: Rola laktoferyny w prawidlowym rozwoju noworodka .Post. Hig.
Med. Dośw., 2005, 59, 421-432
2. Bieńkowska-Haba M.: Tlenek azotu produkowany przez leukocyty płucne w astmie
oskrzelowej. Post. Hig. Med. Dośw., 2005, 59, 584-601
3. Boratyńska M., Rybka K.: Malignant melanoma In a patent with polyomavirus-BKassociated nephropathy. Transpl. Infect. Dis., 2005, 7, 150-153
4. Borysowski J., Weber-Dąbrowska B., Górski A.: Potencjalne zastosowanie bakteriofagów
w świetle obecnego kryzysu antybiotykoterapii. Pol. Arch. Med. Wewn., 2005, 73, 73-78
5. Czerwiński M., Krop-Wątorek A.: CięŜkołańcuchowe przeciwciała rodziny
wielbłądowatych (Camelidae) i ich moŜliwe zastosowania. Post. Hig. Med. Dośw., 2005,
59, 193-202
6. Dembowski J., Wróbel M., Kołodziej A., Zdrojowy R., Niezgoda T., Szydełko T.,
Małkiewicz B, Dębiński P., Wróbel E., Duś D.: DNA content as an advanced disease
predictor in renal cancer. Adv. Clin. Exper. Med., 2005, 14, 42-46
7. Dembowski J., Wróbel M., Kołodziej A., Zdrojowy R., Niezgoda T., Szydełko T.,
Kasprzak J., Małkiewicz B., Wróbel E., Duś D., Dudek K.: Wartość stęŜenia
hemoglobiny, OB i sICAM-1 w ocenie ryzyka powstania przerzutów u chorych na raka
nerki. Ann. Acad. Med. Siles., 2005, 59, 105-110
8. Dłubek D., Witkiewicz W., Lange A.: Szpikowe komórki macierzyste – identyfikacja i
zastosowanie kliniczne. Post. Biol. Komórki, 2005, 32 (suppl. 23), 125-131
9. Drulis-Kawa Z., Weber-Dąbrowska B., Łusiak-Szelachowska M., Doroszkiewicz W.:
Potential possibilities of using phage typing in elimination of multidrug resistant
Staphylococci. Pol. J. Microbiol., 2005, 54, 63-67
10. Dubiel A., Kozdrowski R., Bielas W., Siemieniuch M., Weber-Dąbrowska B., Mulczyk
M.: Wpływ swoistych bakteriofagów na właściwości nasienia knurów zakaŜonych
pałeczką ropy błękitnej. Medicina Veterinaria, 2005, 4(2), 33-40
11. Duś D., Podolak-Dawidziak M:. Multidrug resistance proteins in leukaemias. Adv. Clin.
Exper. Med., 2005, 14, 407-414
12. Frydecka I., Kosmaczewska A.: Zaburzenia ekspresji molekuł szlaku sygnałowego
limfocytów T w chorobach nowotworowych. Acta Haematol. Pol., 2005, 36, Supl. 1,
171-178
13. Gamian A., Picur B., Staniszewska M., Kaczmarek A.: Structural study of advanced
glycation end-product synthesized in the dry reaction at high temperature, 18th Polish
Peptide Symposium, 408 September 2005, Faculty of Chemistry, Publ. University of
Wrocław, 2005, 107-108
14. Gmyrek G.B.: Mobilność a kariera naukowa po doktoracie. Post. Bioch. 2005; 51, z. 4 –
podgląd dostępny w internecie (www.postepybiochemii.pl)
15. Gmyrek G.B.: Sprawozdanie z Letniego Kursu Hodowli Komórek Zwierzęcych. Post.
Bioch. 2005; 51, z 4 - podgląd dostępny w internecie (www.postepybiochemii.pl)
16. Jędryka M., Międzybrodzki R., Gabryś M.: Serum soluble E-cadherin concentration
during surgical and danazol treatment of women with endometriosis. Adv. Clin. Exp.
Med., 2005; 14(4A), 5-9
17. Jędryka M., Międzybrodzki R., Szymaniec S., Gabryś M.: Natural killer cell cytotoxicity
in the presence of the peritoneal fluid from women with different gynecological disorders.
Adv. Clin. Exp. Med. 2005, 14(4A), 15-19
18. Kern J., Czerwiński M., Waśniowska K.: Otrzymywanie i charakterystyka
rekombinowanych postaci antygenu Duffy. Prace Naukowe Studentów Wydziału
Chemicznego Politechniki Wrocławskiej, 2005, 3, 57-61
19. Kłopotowska D., Strządała L. Rola receptora TrkC i neurotrofiny 3 w rozwoju i funkcji
komórek neuralnych. Post. Hig. Med. Dośw. 2005, 59: 517-522
20. Kotowska M.: Zastosowanie metod biologii molekularnej do poszukiwania genów
biosyntezy antybiotyków poliketydowych i peptydowych produkowanych przez
promieniowce. Post. Biochem., 2005, 51, 345-352
21. Krotkiewska B., Buchaniewicz M., Pasek M., Krotkiewski H.: Biosensor BIAcore
application in analysis of a carbohydrate moiety of glycoproteins. Adv. Clin. Exp. Med.,
2005, 14, 897-903
22. Kubik T., Bogunia-Kubik K., Sugisaka M.: Nanotechnology on duty in medical
applications. Curr. Pharm. Biotechnol., 2005, 6(1), 17-33
23. Lenart K. Szyda A., Duś D., Podolak-Dawidziak M.: Kliniczne skutki oporności
wielolekowej w nowotworach. Onkologia w Praktyce Klinicznej, 2005, 1, 18-26
24. Lipiński T., Zuziak E., Gamian A., Górski A.: Występowanie naturalnych przeciwciał
przeciwko bakteriofagom w surowicy ludzkiej. Forum Wrocławskich Mikrobiologów,
Sesja Naukowa, Wrocław, Wyd. IITD, 2005, 85-92
25. Mackiewicz P., Zakrzewska-Czerwińska J., Cebrat S.: Genomika – dziedzina wiedzy XXI
wieku. Biotechnologia , 2005, 3, 7-21
26. Mendyka B., Radek P.P., Wargacka A., Czarny A., Zaczyńska E., Pawlik M.:
Cytoksyczność i mutagenność preparatów zawierających domieszkę estru metyklowego
oleju rzepakowego. Medycyna Środowiskowa, 2005, 8, 139-145
27. Mendyka B., Walkowiak W., Czarny A., Zaczyńska E., Pawlik M., Wargadzka A., Radek
P.: The effect of biodiesel exhaust composition on a human lung cells. Development in
Production and Use of new Agrochemicals 2005. Chemistry for Agriculture vol. 6, pp.
599-606. Edited by H. Górecki, Z. Dobrzański, P. Kafarski. Czech-Pol Trade, Prague,
Brussels.
28. Mieszała M., Epidemiologia Neisseria meningitidis i immunochemiczne zagadnienia
koniugatowych szczepionek przeciw meningokokowych, Nowości Farmakoterapii, 2005,
27, 12-14
29. Mieszała M., Gamian A., Epidemiologia Neisseria meningitidis i immunochemiczne
zagadnienia koniugatowych szczepionek przeciw meningokokowemu zapaleniu opon
mózgowych. Forum Wrocławskich Mikrobiologów, Sesja Naukowa, Wrocław, Wyd.
IITD, 2005, 75-84
30. Międzybrodzki R., Świerkot J., Szechiński J.: Leki stosowane w reumatologii a układ
krąŜenia. Terapia, 2005, 3(2), 6-12
31. Misiuk-Hojło M., Białek-Szymańska A., Agopsowicz K., Jurowska-Liput J., Gorczyca
W., Witkowska D., Kuropatwa M.: Badania immunologiczne w zwyrodnieniu plamki
związanym z wiekiem. Magazyn Okulist, 2005, 2, 4-6
32. Pawlik K., Kotowska M.: Od sekwencji DNA do antybiotyku. Biotechnologia, 2005, 3,
57-74
33. Pełczyńska M, Jaroszewicz I, Świtalska M, Opolski A.: Właściwości biologiczne
kalcytriolu i jego nowych analogów - potencjalne zastosowania terapeutyczne. (Biological
activity of calcitriol and its new analogues - potential therapeutical applications). Post.
Hig. Med. Dośw. , 2005 (online), 59, 129-139
34. Podolak-Dawidziak M., Duś D., Kiełbiński M., Paprocka M.., Wojdat E., Lenart K.,
Szyda A., Haus O., Kuliszkiewicz-Janus M., Duszeńko E., Prajs I., Kuliczkowski K.:
Clinical relevance of multidrug resistance proteins expression in patients with de novo
acute myeloid leukaemia. Adv. Clin. Exper. Med., 2005;14, 1151-1160
35. Potoczek S., Wołowiec D., Jaźwiec D., Waszczuk E., Kapelko-Słowik K., Frydecka I.,
Mazur G., Kuliczkowski K., Paradowski L.: Czynność absorpcyjna błony śluzowej
przewodu pokarmowego chorych na ostrą białaczkę szpikową. Adv. Clin. Exp. Med.,
2005, 14, 273-279
36. Ruban-Ośmiałowska B., Gust B., Chater K., Jakimowicz D., Zakrzewska-Czerwińska J.:
Strategia wykorzystująca PCR i homologiczną rekombinację do wprowadzania mutacji
chromosomalnych u bakterii rodzaju Streptomyces. Post. Mikrobiol., 2005, 44, 29-37
37. Rybka K., Turkiewicz D., Gorczyńska E., Toporski J., Kałwak K., Dyla A., Chybicka A.:
Wczesna identyfikacja zakaŜeń adenowirusami i poliomawirusami metodą PCR u dzieci
po przeszczepieniu komórek krwiotwórczych. Forum Mikrobiologów Wrocławskich
(Sesja Naukowa), 2005, 49-61.
38. Sedlaczek P., Frydecka I., Gryboś M., Harłozińska-Szmyrka A.: ZaleŜności między
stęŜeniem CA-125 i Sil-2Rα w surowicy, płynach, torbieli i/lub wysiękach otrzewnowych
u chorych na nabłonkowe nowotwory jajnika. Adv. Clin. Exp. Med., 2005, 14, 435-443
39. Sochocka M., Błach-Olszewska Z.: Mechanizmy wrodzonej odporności. Post. Hig. Med.
Dośw., 2005, 59, 250-258
40. Sroka Z., Gamian A., Cisowski W.: Niskocząsteczkowe związki przeciwutleniające
pochodzenia naturalnego. Post. Hig. Med. Dośw., 2005, 59, 34-41
41. Szpak A., Gamian A., Otrzymywanie oczyszczonych bakteriofagów i izolacja ich
antygenów białkowych, Prace Naukowe Studentów, Oficyna Wyd. Politechniki
Wrocławskiej, 2005, 3, 1-4.
42. Szymiczek M., Kurowska E., Gorczyca W.A.: Rola arestyn w sygnalizacji wewnątrzkomórkowej. Post. Hig. Med. Dośw., 2005, 59, 324-333
43. Świerkot J., Międzybrodzki R.: Znaczenie metotreksatu w monoterapii i terapiach
złoŜonych u chorych na reumatoidalne zapalnie stawów. Terapia, 2005, 3(2), 46-52
44. Trzeciakiewicz A., Opolski A., Mazur A.: TRPM7 – białko odpowiedzialne za
homeostazę magnezu w komórce. Post. Hig. Med. Dośw. , 2005 (online), 59, 496-502
45. Valles M.A., Balbuena E., Berezin D.B., Bonnett R., Bosch A., Madariaga M.A.,
ElMerouani A., Garabatos J.R., Gomez A.M., Kinchesh P., Koifman O.I, Melero S.,
Molina S., Perez V., Piasecki E., Salgado A., Sanchez J., Tovar N.A., Velasco D.,
Ziółkowski P., Symonowicz K.: Porfiryny do fotodestrukcji lub wykrywania szybko
rosnących komórek za pomocą MRI. Acta Bio-Optica Informat. Med., 2005, 12, 78-86
46. Wysoczańska B., Kańska K., Kuśnierz-Wolska B., Lange J. , Bernatowska E., Lange A.:
Porównanie efektywności przeszczepu komórek krwiotwórczych od dawców rodzinnych i
alternatywnych u dzieci leczonych allogenicznym przeszczepem szpiku. Pediatria Polska,
2005, 80, 6-7, 502-508
47. Zaczyńska E., Klausa E., Błach-Olszewska Z.: Stymulacja wrodzonej odporności leukocytów światłem spolaryzowanym. Forum Mikrobiologów Wrocławskich (Sesja
Naukowa), 2005, 39-47
48. Zakrzewska-Czerwińska J., Mackiewicz P., Zawilak A., Cebrat S.: Wyznaczenie miejsca
inicjacji replikacji na podstawie sekwencji chromosomu bakteryjnego. Biotechnologia,
2005, 3, 91-101
49. Zakrzewska-Czerwińska J.: Applying molecular biological techniques in identifying
microorganisms. Acta Universitatis Nicolai Copernici, Prace Limnologiczne XXV, Nauki
Matematyczno-Przyrodnicze, 2005, 113, 15-19
50. Ziółkowski J., Bonnett R., Valles M.A., Piasecki E., Jeleń M., Bronowicz A., Ziółkowska
J., Symobnowicz K.: Photodynamic therapy of virus-contaminated red blood cell concentrates. Acta Bio-Optica Informat. Med., 2005, 12, 75-77
51. Zimecki M., Artym J.: Proteins from milk and colostrum of potential therapeutic
application. Post. Hig. Med. Dośw., 2005, 59, 309-323
52. śywicka B., Czarny A., Zaczyńska E., Pielka S., Solski L.: The effect of polyester
vascular prostheses on synthesis TNF-α, IFN-γ and NO by human peripheral blood
leukocytes - in vitro. Polimery w Medycynie, 2005, 35 (3), 3-9
Monografie i rozdziały w ksiąŜkach opublikowane:
1. Chełmońska-Soyta A., Wietrzyk J., Opolski A.:. Udział fitoestrogenów w odpowiedzi
immunologicznej i rozwoju chorob autoimmunizacyjnych u ssaków. W: „Weterynaryjna
higiena pasz. Fitoestrogeny – substancje niepoŜądane. Substancje biologicznie aktywneproblemy analityczne”. Wydawnictwo MG Olsztyn, 2005, str.18-25
2. Duś D., Krawczenko A., Kieda C.: IL-7 receptor and microvascular endothelial cells;
Microvascular Research: Biology and Pathology. Elsevier Science (USA) 2005, pp. 2527.
3. Grynkiewicz G., Opolski A.: Phytoestrogens and Their Effects on Cancer. In:
“Carcinogenic and Anticarcinogenic Food Components” (Baer-Dubowska W., Bartoszek
A., Malejka-Giganti D. eds), Series: Chemical & Functional Properties of Food
Components Vol. 8. 2005. 329-350 Taylor & Francis CRC Press. USA.
4. Katzenellenbogen E.: Badania strukturalne lipopolisacharydów Hafnia alvei ze
szczególnym uwzględnieniem wielocukrów O-swoistych, 2005, IITD PAN Wrocław,
ISBN-83-914239-8-0
5. Walisiewicz-Niedbalska W., Lipkowski A.W., Patkowska-Sokoła B., Opolski A., RóŜycki
K.: Otrzymywanie i charakterystyka izomerów kwasu linolowego ze sprzęŜonymi
wiązaniami podwójnymi str 335—353. W: „Enzymatyczna modyfikacja składników
Ŝywności”, praca zbiorowa pod redakcja Edwarda Kołakowskiego, Włodzimierza
Bednarskiego i Stanisława Bieleckiego stron 579, wyd. Akademia Rolnicza w Szczecinie,
2005 rok, ISBN 83-7317-031-6
6. Wietrzyk J., Godlewska J., Chełmońska-Soyta A., Opolski A.: Fitoestrogeny w terapii i
prewencji przeciwnowotworowej. W: „Weterynaryjna higiena pasz. Fitoestrogeny –
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